During the fourth decade of life, the human skeleton begins to lose bone. That is, bone mass decreases in relation to bone volume. Menopause and the associated estrogen deficiency will enhance bone loss in females. It has also been suspected that bone loss is familial, mainly because of the increased prevalence of osteoporosis in relatives, although there are no satisfactory scientific data to support either a familial or a genetic control of bone loss. In long bones, cortical bone is resorbed from the endosteal surface. Because of the thinning of the cortical bone shell, bones lose their mechanical integrity and fracture more readily. The trabecular bone mass of the vertebral column also decreases with age. Vertebral compression fractures and fractures of the femoral neck are the most serious consequences of bone loss. This project deals with the epidemiological, genetic, cross-sectional, longitudinal, and biomechanical aspects of bone loss (1) among the participants of the Baltimore Longitudinal Study of Aging (BLSA), (2) in genetic isolates of the Adriatic Sea Islands of Croatia and the island of Guam in Micronesia, Japan, Central America, Albania and other parts of the world (cross-cultural), (3) in rats.